Immune Therapy Safe in Early Trial

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The latest entry in the burgeoning field of immune checkpoint blockade, the antibody MPDL3280A, was safe and appears effective in several types of advanced cancer.

Note that the molecule under investigation targets a protein called programmed death ligand 1 (PDL1) and had no dose-limiting toxicities, and most adverse events were mild and transient.

WASHINGTON -- The latest entry in the burgeoning field of immune checkpoint blockade was safe and appears effective in several types of advanced cancer, a researcher said here.

The molecule under investigation – an engineered antibody dubbed MPDL3280A – had no dose-limiting toxicities and most adverse events were mild and transient, according to Michael Gordon, MD, of Pinnacle Oncology Hematology in Scottsdale, Ariz.

Only 3 of the 30 patients in the phase I dose-escalation trial suffered grades 3 or 4 adverse events, but no patient stopped treatment because of toxicity, Gordon reported in a late-breaking session at the annual meeting of the American Association for Cancer Research.

While the industry-sponsored study was not aimed at evaluating the efficacy of the antibody, Gordon said several patients had partial responses and stable disease, although study participants were heavily pre-treated, with a median of two previous courses of therapy.

For example, in one patient with stage IV non-small cell lung cancer, he said, the antibody therapy led to a 95% reduction in tumor size.

All told, there were six partial responses by the standard RECIST criteria, according to Gordon, and 10 cases of stable disease. Several responses had lasted more than a year.

The antibody attacks the PD-1/PD-L1 immune checkpoint, which many cancers use to ward off the attacks of killer T cells.

PD-L1 – shorthand for programmed death-ligand 1 – is expressed on the tumor cell surface. When a killer T cell approaches, PD-L1 binds to a molecule on the immune cell surface dubbed PD-1 and essentially turns off the T cell, rendering it harmless.

MPDL3280A is an antibody that blocks PD-L1, preventing it from binding to PD-1 and keeping the killer T cells active, Gordon said. It's one of several molecules under development that have been designed to block either PD-L1 or PD-1.

Attacking the immune checkpoints is "hot stuff," commented Louis Weiner, MD, of Lombardi Comprehensive Cancer Center at Georgetown University here, one of the pioneers of antibody-based treatment strategies for cancer.

"One of the major new directions for cancer therapy is going to be attacking these immune checkpoints, Weiner told MedPage Today. "There are many different pairs like this that can be targeted, and different cancers will probably rely on different checkpoints."

Weiner said he is very familiar with the MPDL3280A antibody: his group is beginning a clinical trial using it, although he was not involved in the study by Gordon and colleagues.

But he noted that molecules other than MPDL3280A are under development that are aimed at the PD-1/PD-L1 interface; they're yielding "dramatic" responses in patients with very advanced and difficult-to-treat cancers.

"It's hard to know which approach is going to be best, but what is clear is that all of these things are working," Weiner said. In fact, results from early tests of the six molecules under development suggest they will be "the most impacting drugs in the next several years in oncology," according to Antoni Ribas, MD, PhD, of the University of California Los Angeles, who was an invited discussant at the session.

The promising results – treatment response rates of 30% to 40% in a variety of advanced and metastatic cancers – also appear to be durable. "These are no longer anecdotes," Ribas said. "These are reproducible results."

The study was supported by Genetech, a memebr of the Roche group. Gordon reported financial links with the company.

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.